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Prevalence of depression and anxiety in Multiple Sclerosis: A systematic review and meta-analysis

  • Rosa E. Boeschoten
    Correspondence
    Corresponding author at: Department of Psychiatry, VU University Medical Center and GGZinGeest. A.J. Ernststraat 1187, 1081 HL Amsterdam, Netherlands.
    Affiliations
    Department of Psychiatry, VU University Medical Center and GGZinGeest, Amsterdam, Netherlands

    EMGO+ Institute for Health and Care Research, VU University, Amsterdam, Netherlands
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  • Annemarie M.J. Braamse
    Affiliations
    Department of Psychiatry, VU University Medical Center and GGZinGeest, Amsterdam, Netherlands

    EMGO+ Institute for Health and Care Research, VU University, Amsterdam, Netherlands
    Search for articles by this author
  • Aartjan T.F. Beekman
    Affiliations
    Department of Psychiatry, VU University Medical Center and GGZinGeest, Amsterdam, Netherlands

    EMGO+ Institute for Health and Care Research, VU University, Amsterdam, Netherlands
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  • Pim Cuijpers
    Affiliations
    EMGO+ Institute for Health and Care Research, VU University, Amsterdam, Netherlands

    Department of Clinical, Neuro and Developmental Psychology, VU University, Amsterdam, Netherlands
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  • Patricia van Oppen
    Affiliations
    Department of Psychiatry, VU University Medical Center and GGZinGeest, Amsterdam, Netherlands

    EMGO+ Institute for Health and Care Research, VU University, Amsterdam, Netherlands
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  • Joost Dekker
    Affiliations
    Department of Psychiatry, VU University Medical Center and GGZinGeest, Amsterdam, Netherlands

    EMGO+ Institute for Health and Care Research, VU University, Amsterdam, Netherlands

    Department of Rehabilitation Medicine, VU University Medical Center, Amsterdam, Netherlands
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  • Bernard M.J. Uitdehaag
    Affiliations
    Department of Neurology, Multiple Sclerosis Center, VU University Medical Center, Amsterdam, Netherlands
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Published:November 29, 2016DOI:https://doi.org/10.1016/j.jns.2016.11.067

      Highlights

      • Data of a large number MS patients showed high prevalence of depression and anxiety.
      • Prevalence of depressive or anxiety symptoms was elevated compared with disorders.
      • Prevalence rates varied considerably between included studies
      • It is important to agree on patient recruitment and definition of depression/anxiety.
      • To improve prevalence estimates we should focus on specific patient characteristics.

      Abstract

      Objective

      Prevalence rates of depression and anxiety in patients with Multiple Sclerosis (MS) vary widely across studies. Aim of this systematic review and meta-analysis was to a) estimate the prevalence of depression and anxiety in MS, and specifically b) explore sources of heterogeneity (assessment method, prevalence period, study quality, recruitment resource, region) by extensive analyses.

      Methods

      A computerized search in PubMed, EMBASE, and PsycINFO for studies on depression and anxiety in MS was performed up to December 2014.

      Results

      Fifty-eight articles with a total sample size of 87,756 MS patients were selected. Pooled mean prevalence was 30.5% (95% CI = 26.3%–35.1%) for depression, and 22.1% (95% CI = 15.2%–31.0%) for anxiety. Prevalence of clinically significant depressive or anxiety symptoms was higher (35% and 34%) compared with disorders (21%; p = 0.001 and 10%; p < 0.001). Prevalence of a depressive disorder was relatively lower in studies from Europe. Anxiety disorder was more prevalent in community-based samples. Sources of high heterogeneity were not revealed.

      Conclusions

      Data of a large number of patients indicate increased prevalence of depression and anxiety in MS. Further research is needed to identify sources of heterogeneity. Issues to consider are the definition of depression and anxiety, patient recruitment, and patient characteristics.

      Abbreviations:

      DSM (Diagnostic and Statistical Manual of Mental disorders), ICD (international classification of diseases), ICPC (international classification of primary care), SCID (structured clinical interview for DSM disorders), CMA (comprehensive meta-analysis), CES-D (center for epidemiological studies depression scale), HADS (hospital anxiety and depression scale), BDI (beck depression inventory), PHQ (patient health questionnaire)

      Keywords

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      References

        • Feinstein A.
        • Magalhaes S.
        • Richard J.-F.
        • Audet B.
        • Moore C.
        The link between multiple sclerosis and depression.
        Nat. Rev. Neurol. 2014; 10: 507-517https://doi.org/10.1038/nrneurol.2014.139
        • Feinstein A.
        Multiple sclerosis and depression.
        Mult. Scler. 2011; 17: 1276-1281https://doi.org/10.1177/1352458511417835
        • Gold S.M.
        • Irwin M.R.
        Depression and immunity: inflammation and depressive symptoms in multiple sclerosis.
        Neurol. Clin. 2006; 24: 507-519https://doi.org/10.1016/j.ncl.2006.03.007
        • Goldman Consensus Group
        The Goldman consensus statement on depression in multiple sclerosis.
        Mult. Scler. 2005; 11: 328-337
        • Feinstein A.
        • Roy P.
        • Lobaugh N.
        • Feinstein K.
        • O'Connor P.
        • Black S.
        Structural brain abnormalities in multiple sclerosis patients with major depression.
        Neurology. 2004; 62: 586-590
        • Katon W.
        • Lin E.H.B.
        • Kroenke K.
        The association of depression and anxiety with medical symptom burden in patients with chronic medical illness.
        Gen. Hosp. Psychiatry. 2007; 29: 147-155https://doi.org/10.1016/j.genhosppsych.2006.11.005
        • Mohr D.C.
        • Goodkin D.E.
        • Likosky W.
        • Gatto N.
        • Baumann K.A.
        • Rudick R.A.
        Treatment of depression improves adherence to interferon beta-1b therapy for multiple sclerosis.
        Arch. Neurol. 1997; 54: 531-533
        • Fruehwald S.
        • Loeffler-Stastka H.
        • Eher R.
        • Saletu B.
        • Baumhackl U.
        Depression and quality of life in multiple sclerosis.
        Acta Neurol. Scand. 2001; 104: 257-261
        • Minden S.L.
        • Feinstein A.
        • Kalb R.C.
        • Miller D.
        • Mohr D.C.
        • Patten S.B.
        • Bever C.
        • Schiffer R.B.
        • Gronseth G.S.
        • Narayanaswami P.
        Guideline development Subcommittee of the American Academy of neurology, evidence-based guideline: assessment and management of psychiatric disorders in individuals with MS: report of the guideline development Subcommittee of the American Academy of neurology.
        Neurology. 2014; 82: 174-181https://doi.org/10.1212/WNL.0000000000000013
        • Hind D.
        • Cotter J.
        • Thake A.
        • Bradburn M.
        • Cooper C.
        • Isaac C.
        • House A.
        Cognitive behavioural therapy for the treatment of depression in people with multiple sclerosis: a systematic review and meta-analysis.
        BMC Psychiatry. 2014; 14: 5https://doi.org/10.1186/1471-244X-14-5
        • Koch M.W.
        • Patten S.
        • Berzins S.
        • Zhornitsky S.
        • Greenfield J.
        • Wall W.
        • Metz L.M.
        Depression in multiple sclerosis: a long-term longitudinal study.
        Mult. Scler. 2015; 21: 76-82https://doi.org/10.1177/1352458514536086
        • Siegert R.J.
        • Abernethy D.A.
        Depression in multiple sclerosis: a review.
        J. Neurol. Neurosurg. Psychiatry. 2005; 76: 469-475https://doi.org/10.1136/jnnp.2004.054635
        • Patten S.B.
        • Metz L.M.
        Depression in multiple sclerosis.
        Psychother. Psychosom. 1997; 66: 286-292
        • Marrie R.A.
        • Reingold S.
        • Cohen J.
        • Stuve O.
        • Trojano M.
        • Sorensen P.S.
        • Cutter G.
        • Reider N.
        The incidence and prevalence of psychiatric disorders in multiple sclerosis: a systematic review.
        Mult. Scler. 2015; 21: 305-317https://doi.org/10.1177/1352458514564487
        • Creed F.
        • Dickens C.
        Depression in the medically ill.
        in: Steptoe A. Depress. Phys. Illn. Cambridge University Press, 2007: 3-19
        • Ehde D.M.
        • Bombardier C.H.
        Depression in persons with multiple sclerosis.
        Phys. Med. Rehabil. Clin. N. Am. 2005; 16: 437-448https://doi.org/10.1016/j.pmr.2005.01.010
        • Patten S.B.
        • Beck C.A.
        • Williams J.V.A.
        • Barbui C.
        • Metz L.M.
        Major depression in multiple sclerosis: a population-based perspective.
        Neurology. 2003; 61: 1524-1527
      1. Higgins JPT, Green S, Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011], The Cochrane Collaboration, 2011. (Available from) www.handbook.cochrane.org., n.d.

        • American Psychiatric Association
        Diagnostic and Statistical Manual of Mental Disorders (DSM-IV).
        fourth ed. American Psychiatric Press, Washington1994
        • World Health Organization
        The ICD-10 Classification of Mental and Behavioural Disorders: Diagnostic Criteria for Research.
        World Health Organization, Geneva1993
        • World Health Organization
        International Classification of Primary Care.
        2th ed. World Health Organization, Geneva2011 (ICPC-2)
        • Pozzilli C.
        • Schweikert B.
        • Ecari U.
        • Oentrich W.
        BetaPlus study group, supportive strategies to improve adherence to IFN β-1b in multiple sclerosis–results of the βPlus observational cohort study.
        J. Neurol. Sci. 2011; 307: 120-126https://doi.org/10.1016/j.jns.2011.04.026
        • Marrie R.A.
        • Cutter G.
        • Tyry T.
        • Campagnolo D.
        • Vollmer T.
        Smoking status over two years in patients with multiple sclerosis.
        Neuroepidemiology. 2009; 32: 72-79https://doi.org/10.1159/000170910
        • Cetin K.
        • Johnson K.L.
        • Ehde D.M.
        • Kuehn C.M.
        • Amtmann D.
        • Kraft G.H.
        Antidepressant use in multiple sclerosis: epidemiologic study of a large community sample.
        Mult. Scler. 2007; 13: 1046-1053https://doi.org/10.1177/1352458507077864
        • Turner A.P.
        • Williams R.M.
        • Bowen J.D.
        • Kivlahan D.R.
        • Haselkorn J.K.
        Suicidal ideation in multiple sclerosis.
        Arch. Phys. Med. Rehabil. 2006; 87: 1073-1078https://doi.org/10.1016/j.apmr.2006.04.021
        • Mohr D.C.
        • Hart S.L.
        • Fonareva I.
        • Tasch E.S.
        Treatment of depression for patients with multiple sclerosis in neurology clinics.
        Mult. Scler. 2006; 12: 204-208
        • Chwastiak L.A.
        • Gibbons L.E.
        • Ehde D.M.
        • Sullivan M.
        • Bowen J.D.
        • Bombardier C.H.
        • Kraft G.H.
        Fatigue and psychiatric illness in a large community sample of persons with multiple sclerosis.
        J. Psychosom. Res. 2005; 59: 291-298https://doi.org/10.1016/j.jpsychores.2005.06.001
        • McGuigan C.
        • Hutchinson M.
        Unrecognised symptoms of depression in a community-based population with multiple sclerosis.
        J. Neurol. 2006; 253: 219-223https://doi.org/10.1007/s00415-005-0963-0
        • Bombardier C.H.
        • Blake K.D.
        • Ehde D.M.
        • Gibbons L.E.
        • Moore D.
        • Kraft G.H.
        Alcohol and drug abuse among persons with multiple sclerosis.
        Mult. Scler. 2004; 10: 35-40
        • Ehde D.M.
        • Gibbons L.E.
        • Chwastiak L.
        • Bombardier C.H.
        • Sullivan M.D.
        • Kraft G.H.
        Chronic pain in a large community sample of persons with multiple sclerosis.
        Mult. Scler. 2003; 9: 605-611
        • Buchanan R.J.
        • Wang S.
        • Ju H.
        Analyses of the minimum data set: comparisons of nursing home residents with multiple sclerosis to other nursing home residents.
        Mult. Scler. 2002; 8: 512-522
        • Chwastiak L.
        • Ehde D.M.
        • Gibbons L.E.
        • Sullivan M.
        • Bowen J.D.
        • Kraft G.H.
        Depressive symptoms and severity of illness in multiple sclerosis: epidemiologic study of a large community sample.
        Am. J. Psychiatry. 2002; 159: 1862-1868https://doi.org/10.1176/appi.ajp.159.11.1862
        • Carta M.G.
        • Moro M.F.
        • Lorefice L.
        • Picardi A.
        • Trincas G.
        • Fenu G.
        • Cocco E.
        • Floris F.
        • Bessonov D.
        • Akiskal H.S.
        • Marrosu M.G.
        Multiple sclerosis and bipolar disorders: the burden of comorbidity and its consequences on quality of life.
        J. Affect. Disord. 2014; 167: 192-197https://doi.org/10.1016/j.jad.2014.05.024
        • Marrie R.A.
        • Fisk J.D.
        • Stadnyk K.J.
        • Tremlett H.
        • Wolfson C.
        • Warren S.
        • Bhan V.
        • Yu B.N.
        CIHR team in the epidemiology and impact of comorbidity on multiple sclerosis, performance of administrative case definitions for comorbidity in multiple sclerosis in Manitoba and Nova Scotia.
        Chronic Dis. Inj. Can. 2014; 34: 145-153
        • Ostacoli L.
        • Carletto S.
        • Borghi M.
        • Cavallo M.
        • Rocci E.
        • Zuffranieri M.
        • Malucchi S.
        • Bertolotto A.
        • Zennaro A.
        • Furlan P.M.
        • Picci R.L.
        Prevalence and significant determinants of post-traumatic stress disorder in a large sample of patients with multiple sclerosis.
        J. Clin. Psychol. Med. Settings. 2013; 20: 240-246https://doi.org/10.1007/s10880-012-9323-2
        • Hoy D.
        • Brooks P.
        • Woolf A.
        • Blyth F.
        • March L.
        • Bain C.
        • Baker P.
        • Smith E.
        • Buchbinder R.
        Assessing risk of bias in prevalence studies: modification of an existing tool and evidence of interrater agreement.
        J. Clin. Epidemiol. 2012; 65: 934-939https://doi.org/10.1016/j.jclinepi.2011.11.014
        • Higgins J.P.T.
        • Thompson S.G.
        • Deeks J.J.
        • Altman D.G.
        Measuring inconsistency in meta-analyses.
        BMJ. 2003; 327: 557-560https://doi.org/10.1136/bmj.327.7414.557
        • Borenstein M.
        • Hedges L.V.
        • Higgins J.P.T.
        • Rothstein H.R.
        Introduction to Meta-Analysis.
        Wiley, 2009
        • Amtmann D.
        • Kim J.
        • Chung H.
        • Bamer A.M.
        • Askew R.L.
        • Wu S.
        • Cook K.F.
        • Johnson K.L.
        Comparing CESD-10, PHQ-9, and PROMIS depression instruments in individuals with multiple sclerosis.
        Rehabil. Psychol. 2014; 59: 220-229https://doi.org/10.1037/a0035919
        • Asano M.
        • Duquette P.
        • Andersen R.
        • Lapierre Y.
        • Mayo N.E.
        Exercise barriers and preferences among women and men with multiple sclerosis.
        Disabil. Rehabil. 2013; 35: 353-361https://doi.org/10.3109/09638288.2012.742574
        • Bamer A.M.
        • Cetin K.
        • Johnson K.L.
        • Gibbons L.E.
        • Ehde D.M.
        Validation study of prevalence and correlates of depressive symptomatology in multiple sclerosis.
        Gen. Hosp. Psychiatry. 2008; 30: 311-317https://doi.org/10.1016/j.genhosppsych.2008.04.006
        • Beal C.
        • Stuifbergen A.K.
        • Sands D.V.
        • Brown A.
        Depression in multiple sclerosis: a longitudinal analysis.
        Arch. Psychiatr. Nurs. 2007; 21: 181-191https://doi.org/10.1016/j.apnu.2007.02.008
        • Brenner P.
        • Alexanderson K.
        • Björkenstam C.
        • Hillert J.
        • Jokinen J.
        • Mittendorfer-Rutz E.
        • Tinghög P.
        Psychiatric diagnoses, medication and risk for disability pension in multiple sclerosis patients; a population-based register study.
        PLoS One. 2014; 9e104165https://doi.org/10.1371/journal.pone.0104165
        • Buchanan R.J.
        • Wang S.
        • Tai-Seale M.
        • Ju H.
        Analyses of nursing home residents with multiple sclerosis and depression using the minimum data set.
        Mult. Scler. 2003; 9: 171-188
        • Carta M.G.
        • Moro M.F.
        • Lorefice L.
        • Trincas G.
        • Cocco E.
        • Del Giudice E.
        • Fenu G.
        • Colom F.
        • Marrosu M.G.
        The risk of bipolar disorders in multiple sclerosis.
        J. Affect. Disord. 2014; 155: 255-260https://doi.org/10.1016/j.jad.2013.11.008
        • Coyle P.K.
        • Cohen B.A.
        • Leist T.
        • Markowitz C.
        • Oleen-Burkey M.
        • Schwartz M.
        • Tullman M.J.
        • Zwibel H.
        Therapy optimization in multiple sclerosis: a prospective observational study of therapy compliance and outcomes.
        BMC Neurol. 2014; 14: 49https://doi.org/10.1186/1471-2377-14-49
        • da Silva A.M.
        • Vilhena E.
        • Lopes A.
        • Santos E.
        • Gonçalves M.A.
        • Pinto C.
        • Moreira I.
        • Mendonça D.
        • Cavaco S.
        Depression and anxiety in a Portuguese MS population: associations with physical disability and severity of disease.
        J. Neurol. Sci. 2011; 306: 66-70https://doi.org/10.1016/j.jns.2011.03.042
        • Demakis G.J.
        • Buchanan R.
        • Dewald L.
        A longitudinal study of cognition in nursing home residents with multiple sclerosis.
        Disabil. Rehabil. 2009; 31: 1734-1741https://doi.org/10.1080/09638280902738664
        • Duquin J.A.
        • Parmenter B.A.
        • Benedict R.H.B.
        Influence of recruitment and participation bias in neuropsychological research among MS patients.
        J. Int. Neuropsychol. Soc. 2008; 14: 494-498https://doi.org/10.1017/S1355617708080624
        • Ensari I.
        • Motl R.W.
        • McAuley E.
        • Mullen S.P.
        • Feinstein A.
        Patterns and predictors of naturally occurring change in depressive symptoms over a 30-month period in multiple sclerosis.
        Mult. Scler. 2014; 20: 602-609https://doi.org/10.1177/1352458513504251
        • Ferrando S.J.
        • Samton J.
        • Mor N.
        • Nicora S.
        • Findler M.
        • Apatoff B.
        Patient health questionnaire-9 to screen for depression in outpatients with multiple sclerosis.
        Int. J. MS Care. 2007; 9: 99-103https://doi.org/10.7224/1537-2073-9.3.99
        • Hakim E.A.
        • Bakheit A.M.
        • Bryant T.N.
        • Roberts M.W.
        • McIntosh-Michaelis S.A.
        • Spackman A.J.
        • Martin J.P.
        • McLellan D.L.
        The social impact of multiple sclerosis–a study of 305 patients and their relatives.
        Disabil. Rehabil. 2000; 22: 288-293
        • Harel Y.
        • Barak Y.
        • Achiron A.
        Dysregulation of affect in multiple sclerosis: new phenomenological approach.
        Psychiatry Clin. Neurosci. 2007; 61: 94-98https://doi.org/10.1111/j.1440-1819.2007.01616.x
        • van der Hiele K.
        • Spliethoff-Kamminga N.G.
        • Ruimschotel R.P.
        • Middelkoop H.A.
        • Visser L.H.
        Daily hassles reported by Dutch multiple sclerosis patients.
        J. Neurol. Sci. 2012; 320: 85-90https://doi.org/10.1016/j.jns.2012.06.023
        • Holden K.
        • Isaac C.L.
        Depression in multiple sclerosis: reactive or endogenous?.
        Clin. Neuropsychol. 2011; 25: 624-639https://doi.org/10.1080/13854046.2011.564208
        • Horton M.
        • Rudick R.A.
        • Hara-Cleaver C.
        • Marrie R.A.
        Validation of a self-report comorbidity questionnaire for multiple sclerosis.
        Neuroepidemiology. 2010; 35: 83-90https://doi.org/10.1159/000311013
        • Jensen M.P.
        • Smith A.E.
        • Bombardier C.H.
        • Yorkston K.M.
        • Miró J.
        • Molton I.R.
        Social support, depression, and physical disability: age and diagnostic group effects.
        Disabil. Health J. 2014; 7: 164-172https://doi.org/10.1016/j.dhjo.2013.11.001
        • Johansson S.
        • Ytterberg C.
        • Claesson I.M.
        • Lindberg J.
        • Hillert J.
        • Andersson M.
        • Widén Holmqvist L.
        • von Koch L.
        High concurrent presence of disability in multiple sclerosis. Associations with perceived health.
        J. Neurol. 2007; 254: 767-773https://doi.org/10.1007/s00415-006-0431-5
        • Jones K.H.
        • Ford D.V.
        • Jones P.A.
        • John A.
        • Middleton R.M.
        • Lockhart-Jones H.
        • Osborne L.A.
        • Noble J.G.
        A large-scale study of anxiety and depression in people with multiple sclerosis: a survey via the web portal of the UK MS register.
        PLoS One. 2012; 7e41910https://doi.org/10.1371/journal.pone.0041910
        • Kang J.H.
        • Chen Y.H.
        • Lin H.C.
        Comorbidities amongst patients with multiple sclerosis: a population-based controlled study.
        Eur. J. Neurol. 2010; 17: 1215-1219https://doi.org/10.1111/j.1468-1331.2010.02971.x
        • Kargarfard M.
        • Eetemadifar M.
        • Mehrabi M.
        • Maghzi A.H.
        • Hayatbakhsh M.R.
        Fatigue, depression, and health-related quality of life in patients with multiple sclerosis in Isfahan, Iran.
        Eur. J. Neurol. 2012; 19: 431-437https://doi.org/10.1111/j.1468-1331.2011.03535.x
        • Kehler M.D.
        • Hadjistavropoulos H.D.
        Is health anxiety a significant problem for individuals with multiple sclerosis?.
        J. Behav. Med. 2009; 32: 150-161https://doi.org/10.1007/s10865-008-9186-z
        • Lo Fermo S.
        • Barone R.
        • Patti F.
        • Laisa P.
        • Cavallaro T.L.
        • Nicoletti A.
        • Zappia M.
        Outcome of psychiatric symptoms presenting at onset of multiple sclerosis: a retrospective study.
        Mult. Scler. 2010; 16: 742-748https://doi.org/10.1177/1352458510365157
        • Lobentanz I.S.
        • Asenbaum S.
        • Vass K.
        • Sauter C.
        • Klösch G.
        • Kollegger H.
        • Kristoferitsch W.
        • Zeitlhofer J.
        Factors influencing quality of life in multiple sclerosis patients: disability, depressive mood, fatigue and sleep quality.
        Acta Neurol. Scand. 2004; 110: 6-13https://doi.org/10.1111/j.1600-0404.2004.00257
        • Marrie R.A.
        • Fisk J.D.
        • Yu B.N.
        • Leung S.
        • Elliott L.
        • Caetano P.
        • Warren S.
        • Evans C.
        • Wolfson C.
        • Svenson L.W.
        • Tremlett H.
        • Blanchard J.F.
        • Patten S.B.
        CIHR team in the epidemiology and impact of comorbidity on multiple sclerosis, mental comorbidity and multiple sclerosis: validating administrative data to support population-based surveillance.
        BMC Neurol. 2013; 13: 16https://doi.org/10.1186/1471-2377-13-16
        • Mattioli F.
        • Bellomi F.
        • Stampatori C.
        • Parrinello G.
        • Capra R.
        Depression, disability and cognitive impairment in multiple sclerosis: a cross sectional Italian study.
        Neurol. Sci. Off. J. Ital. Neurol. Soc. Ital. Soc. Clin. Neurophysiol. 2011; 32: 825-832https://doi.org/10.1007/s10072-011-0624-2
        • Mohr D.C.
        • Hart S.L.
        • Julian L.
        • Tasch E.S.
        Screening for depression among patients with multiple sclerosis: two questions may be enough.
        Mult. Scler. 2007; 13: 215-219https://doi.org/10.1177/1352458506070926
        • Moreau T.
        • Schmidt N.
        • Joyeux O.
        • Bungener C.
        • Souvignet V.
        Coping strategy and anxiety evolution in multiple sclerosis patients initiating interferon-beta treatment.
        Eur. Neurol. 2009; 62: 79-85https://doi.org/10.1159/000222777
        • Neau J.P.
        • Paquereau J.
        • Auche V.
        • Mathis S.
        • Godeneche G.
        • Ciron J.
        • Moinot N.
        • Bouche G.
        Sleep disorders and multiple sclerosis: a clinical and polysomnography study.
        Eur. Neurol. 2012; 68: 8-15https://doi.org/10.1159/000335076
        • Nuyen J.
        • Schellevis F.G.
        • Satariano W.A.
        • Spreeuwenberg P.M.
        • Birkner M.D.
        • van den Bos G.A.M.
        • Groenewegen P.P.
        Comorbidity was associated with neurologic and psychiatric diseases: a general practice-based controlled study.
        J. Clin. Epidemiol. 2006; 59: 1274-1284https://doi.org/10.1016/j.jclinepi.2006.01.005
        • Patten S.B.
        • Williams J.V.A.
        • Lavorato D.H.
        • Koch M.
        • Metz L.M.
        Depression as a predictor of occupational transition in a multiple sclerosis cohort.
        Funct. Neurol. 2013; 28: 275-280
        • Patten S.B.
        • Svenson L.W.
        • Metz L.M.
        Descriptive epidemiology of affective disorders in multiple sclerosis.
        CNS Spectr. 2005; 10: 365-371
        • Patten S.B.
        • Lavorato D.H.
        • Metz L.M.
        Clinical correlates of CES-D depressive symptom ratings in an MS population.
        Gen. Hosp. Psychiatry. 2005; 27: 439-445https://doi.org/10.1016/j.genhosppsych.2005.06.010
        • Patten S.B.
        • Berzins S.
        • Metz L.M.
        Challenges in screening for depression in multiple sclerosis.
        Mult. Scler. 2010; 16: 1406-1411https://doi.org/10.1177/1352458510377770
        • Patti F.
        • Amato M.P.
        • Battaglia M.A.
        • Pitaro M.
        • Russo P.
        • Solaro C.
        • Trojano M.
        Caregiver quality of life in multiple sclerosis: a multicentre Italian study.
        Mult. Scler. 2007; 13: 412-419https://doi.org/10.1177/1352458506070707
        • Patti F.
        • Pozzilli C.
        • Montanari E.
        • Pappalardo A.
        • Piazza L.
        • Levi A.
        • Onesti E.
        • Pesci I.
        Italian study group on quality of life in Ms, effects of education level and employment status on HRQoL in early relapsing-remitting multiple sclerosis.
        Mult. Scler. 2007; 13: 783-791https://doi.org/10.1177/1352458506073511
        • Pittion-Vouyovitch S.
        • Debouverie M.
        • Guillemin F.
        • Vandenberghe N.
        • Anxionnat R.
        • Vespignani H.
        Fatigue in multiple sclerosis is related to disability, depression and quality of life.
        J. Neurol. Sci. 2006; 243: 39-45https://doi.org/10.1016/j.jns.2005.11.025
        • Poder K.
        • Ghatavi K.
        • Fisk J.D.
        • Campbell T.L.
        • Kisely S.
        • Sarty I.
        • Stadnyk K.
        • Bhan V.
        Social anxiety in a multiple sclerosis clinic population.
        Mult. Scler. 2009; 15: 393-398https://doi.org/10.1177/1352458508099143
        • Porcel J.
        • Río J.
        • Sánchez-Betancourt A.
        • Arévalo M.J.
        • Tintoré M.
        • Téllez N.
        • Borràs C.
        • Nos C.
        • Montalbán X.
        Long-term emotional state of multiple sclerosis patients treated with interferon beta.
        Mult. Scler. 2006; 12: 802-807
        • Pozzilli C.
        • Schweikert B.
        • Ecari U.
        • Oentrich W.
        • Bugge J.-P.
        Quality of life and depression in multiple sclerosis patients: longitudinal results of the BetaPlus study.
        J. Neurol. 2012; 259: 2319-2328https://doi.org/10.1007/s00415-012-6492-8
        • Sadovnick A.D.
        • Remick R.A.
        • Allen J.
        • Swartz E.
        • Yee I.M.
        • Eisen K.
        • Farquhar R.
        • Hashimoto S.A.
        • Hooge J.
        • Kastrukoff L.F.
        • Morrison W.
        • Nelson J.
        • Oger J.
        • Paty D.W.
        Depression and multiple sclerosis.
        Neurology. 1996; 46: 628-632
        • Simpson R.J.
        • McLean G.
        • Guthrie B.
        • Mair F.
        • Mercer S.W.
        Physical and mental health comorbidity is common in people with multiple sclerosis: nationally representative cross-sectional population database analysis.
        BMC Neurol. 2014; 14: 128https://doi.org/10.1186/1471-2377-14-128
        • Solari A.
        • Motta A.
        • Mendozzi L.
        • Aridon P.
        • Bergamaschi R.
        • Ghezzi A.
        • Mancardi G.L.
        • Milanese C.
        • Montanari E.
        • Pucci E.
        Italian version of the Chicago multiscale depression inventory: translation, adaptation and testing in people with multiple sclerosis.
        Neurol. Sci. Off. J. Ital. Neurol. Soc. Ital. Soc. Clin. Neurophysiol. 2004; 24: 375-383https://doi.org/10.1007/s10072-003-0192-1
        • Sollom A.C.
        • Kneebone I.I.
        Treatment of depression in people who have multiple sclerosis.
        Mult. Scler. 2007; 13: 632-635https://doi.org/10.1177/1352458507072384
        • Somerset M.
        • Campbell R.
        • Sharp D.J.
        • Peters T.J.
        What do people with MS want and expect from health-care services?.
        Health Expect. Int. J. Public Particip. Health Care Health Policy. 2001; 4: 29-37
        • Spain L.A.
        • Tubridy N.
        • Kilpatrick T.J.
        • Adams S.J.
        • Holmes A.C.N.
        Illness perception and health-related quality of life in multiple sclerosis.
        Acta Neurol. Scand. 2007; 116: 293-299https://doi.org/10.1111/j.1600-0404.2007.00895
        • Stepleman L.M.
        • Decker M.
        • Rollock M.
        • Casillas R.
        • Brands T.
        Depression screening in Black Americans with multiple sclerosis.
        Psychol. Health Med. 2014; 19: 33-39https://doi.org/10.1080/13548506.2013.775466
        • Thielscher C.
        • Thielscher S.
        • Kostev K.
        The risk of developing depression when suffering from neurological diseases.
        GMS Ger. Med. Sci. 2013; 11https://doi.org/10.3205/000170
        • Viner R.
        • Fiest K.M.
        • Bulloch A.G.M.
        • Williams J.V.A.
        • Lavorato D.H.
        • Berzins S.
        • Jetté N.
        • Metz L.M.
        • Patten S.B.
        Point prevalence and correlates of depression in a national community sample with multiple sclerosis.
        Gen. Hosp. Psychiatry. 2014; 36: 352-354https://doi.org/10.1016/j.genhosppsych.2013.12.011
        • Verdier-Taillefer M.H.
        • Gourlet V.
        • Fuhrer R.
        • Alpérovitch A.
        Psychometric properties of the Center for Epidemiologic Studies-Depression scale in multiple sclerosis.
        Neuroepidemiology. 2001; 20 (doi: 54800): 262-267
        • Williams R.M.
        • Turner A.P.
        • Hatzakis M.
        • Bowen J.D.
        • Rodriquez A.A.
        • Haselkorn J.K.
        Prevalence and correlates of depression among veterans with multiple sclerosis.
        Neurology. 2005; 64: 75-80https://doi.org/10.1212/01.WNL.0000148480.31424.2A
        • Zettl U.K.
        • Bauer-Steinhusen U.
        • Glaser T.
        • Hechenbichler K.
        • Limmroth V.
        Study group, evaluation of an electronic diary for improvement of adherence to interferon beta-1b in patients with multiple sclerosis: design and baseline results of an observational cohort study.
        BMC Neurol. 2013; 13: 117https://doi.org/10.1186/1471-2377-13-117
        • Marrie R.A.
        • Horwitz R.
        • Cutter G.
        • Tyry T.
        • Campagnolo D.
        • Vollmer T.
        The burden of mental comorbidity in multiple sclerosis: frequent, underdiagnosed, and undertreated.
        Mult. Scler. 2009; 15: 385-392https://doi.org/10.1177/1352458508099477
        • Radloff L.S.
        The CES-D scale a self-report depression scale for research in the general population.
        Appl. Psychol. Meas. 1977; 1: 385-401https://doi.org/10.1177/014662167700100306
        • Zigmond A.S.
        • Snaith R.P.
        The hospital anxiety and depression scale.
        Acta Psychiatr. Scand. 1983; 67: 361-370https://doi.org/10.1111/j.1600-0447.1983.tb09716.x
        • Beck A.T.
        • Ward C.H.
        • Mendelson M.
        • et al.
        An inventory for measuring depression.
        Arch. Gen. Psychiatry. 1961; 53–63
        • Löwe B.
        • Kroenke K.
        • Herzog W.
        • Gräfe K.
        Measuring depression outcome with a brief self-report instrument: sensitivity to change of the patient health questionnaire (PHQ-9).
        J. Affect. Disord. 2004; 81: 61-66https://doi.org/10.1016/S0165-0327(03)00198-8
        • Beck A.T.
        • Steer R.A.
        Beck depression inventory manual.
        Psychological Corporation, San Antonio1993
        • Bromet E.
        • Andrade L.H.
        • Hwang I.
        • Sampson N.A.
        • Alonso J.
        • de Girolamo G.
        • de Graaf R.
        • Demyttenaere K.
        • Hu C.
        • Iwata N.
        • Karam A.N.
        • Kaur J.
        • Kostyuchenko S.
        • Lépine J.-P.
        • Levinson D.
        • Matschinger H.
        • Mora M.E.M.
        • Browne M.O.
        • Posada-Villa J.
        • Viana M.C.
        • Williams D.R.
        • Kessler R.C.
        Cross-national epidemiology of DSM-IV major depressive episode.
        BMC Med. 2011; 9: 90https://doi.org/10.1186/1741-7015-9-90
        • Kessler R.C.
        The costs of depression.
        Psychiatr. Clin. N. Am. 2012; 35: 1-14https://doi.org/10.1016/j.psc.2011.11.005
        • de Graaf R.
        • ten Have M.
        • van Gool C.
        • van Dorsselaer S.
        Prevalence of mental disorders and trends from 1996 to 2009. Results from the Netherlands mental health survey and incidence study-2.
        Soc. Psychiatry Psychiatr. Epidemiol. 2012; 47: 203-213https://doi.org/10.1007/s00127-010-0334-8
        • Dahl O.P.
        • Stordal E.
        • Lydersen S.
        • Midgard R.
        Anxiety and depression in multiple sclerosis. A comparative population-based study in Nord-Trøndelag County, Norway.
        Mult. Scler. 2009; 15: 1495-1501https://doi.org/10.1177/1352458509351542
        • Patten S.B.
        • Schopflocher D.
        Longitudinal epidemiology of major depression as assessed by the brief patient health questionnaire (PHQ-9).
        Compr. Psychiatry. 2009; 50: 26-33https://doi.org/10.1016/j.comppsych.2008.05.012
        • Reijnders J.S.A.M.
        • Ehrt U.
        • Weber W.E.J.
        • Aarsland D.
        • Leentjens A.F.G.
        A systematic review of prevalence studies of depression in Parkinson's disease.
        Mov. Disord. 2008; 23: 183-189https://doi.org/10.1002/mds.21803
        • Anderson R.J.
        • Freedland K.E.
        • Clouse R.E.
        • Lustman P.J.
        The prevalence of comorbid depression in adults with diabetes: a meta-analysis.
        Diabetes Care. 2001; 24: 1069-1078
        • Grigsby A.B.
        • Anderson R.J.
        • Freedland K.E.
        • Clouse R.E.
        • Lustman P.J.
        Prevalence of anxiety in adults with diabetes: a systematic review.
        J. Psychosom. Res. 2002; 53: 1053-1060
        • Kessler R.C.
        • Aguilar-Gaxiola S.
        • Alonso J.
        • Chatterji S.
        • Lee S.
        • Ormel J.
        • Üstün T.B.
        • Wang P.S.
        The global burden of mental disorders: an update from the WHO world mental health (WMH) surveys.
        Epidemiol. Psychiatr. Sci. 2009; 18: 23-33https://doi.org/10.1017/S1121189X00001421
        • Hasselmann H.
        • Bellmann-Strobl J.
        • Ricken R.
        • Oberwahrenbrock T.
        • Rose M.
        • Otte C.
        • Adli M.
        • Paul F.
        • Brandt A.U.
        • Finke C.
        • Gold S.M.
        Characterizing the phenotype of multiple sclerosis-associated depression in comparison with idiopathic major depression.
        Mult. Scler. 2016; 22: 1476-1484https://doi.org/10.1177/1352458515622826
        • Patten S.B.
        • Burton J.M.
        • Fiest K.M.
        • Wiebe S.
        • Bulloch A.G.M.
        • Koch M.
        • Dobson K.S.
        • Metz L.M.
        • Maxwell C.J.
        • Jetté N.
        Validity of four screening scales for major depression in MS.
        Mult. Scler. 2015; 21: 1064-1071https://doi.org/10.1177/1352458514559297
        • Fischer A.
        • Fischer M.
        • Nicholls R.A.
        • Lau S.
        • Poettgen J.
        • Patas K.
        • Heesen C.
        • Gold S.M.
        Diagnostic accuracy for major depression in multiple sclerosis using self-report questionnaires.
        Brain Behav. 2015; 5e00365https://doi.org/10.1002/brb3.365
        • Rush A.J.
        • Gullion C.M.
        • Basco M.R.
        • Jarrett R.B.
        • Trivedi M.H.
        The inventory of depressive symptomatology (IDS): psychometric properties.
        Psychol. Med. 1996; 26: 477-486
        • Beck A.T.
        • Steer R.A.
        • Brown G.K.
        The Beck Depression Inventory.
        second ed. 78204-2498. 1996 (Manual, San Antonio, TX)
        • Khan A.Y.
        • Carrithers J.
        • Preskorn S.H.
        • Lear R.
        • Wisniewski S.R.
        • Rush A.J.
        • Stegman D.
        • Kelley C.
        • Kreiner K.
        • Nierenberg A.A.
        • Fava M.
        Clinical and demographic factors associated with DSM-IV melancholic depression.
        Ann. Clin. Psychiatry. 2006; 18: 91-98https://doi.org/10.3109/10401230600614496
        • Novick J.S.
        • Stewart J.W.
        • Wisniewski S.R.
        • Cook I.A.
        • Manev R.
        • Nierenberg A.A.
        • Rosenbaum J.F.
        • Shores-Wilson K.
        • Balasubramani G.K.
        • Biggs M.M.
        Clinical and demographic features of atypical depression in outpatients with major depressive disorder: preliminary findings from STAR*D.[CME].
        J. Clin. Psychiatry. 2005; 66: 1002-1011
        • Lamers F.
        • Vogelzangs N.
        • Merikangas K.R.
        • de Jonge P.
        • Beekman A.T.F.
        • Penninx B.W.J.H.
        Evidence for a differential role of HPA-axis function, inflammation and metabolic syndrome in melancholic versus atypical depression.
        Mol. Psychiatry. 2013; 18: 692-699https://doi.org/10.1038/mp.2012.144
        • Dunn G.
        • Pickles A.
        • Tansella M.
        • Vázquez-Barquero J.L.
        Two-phase epidemiological surveys in psychiatric research.
        Br. J. Psychiatry J. Ment. Sci. 1999; 174: 95-100
        • Marrie R.A.
        • Miller A.
        • Sormani M.P.
        • Thompson A.
        • Waubant E.
        • Trojano M.
        • O'Connor P.
        • Fiest K.
        • Reider N.
        • Reingold S.
        • Cohen J.A.
        • Attendees of the International Workshop on Comorbidity in Multiple Sclerosis
        Recommendations for observational studies of comorbidity in multiple sclerosis.
        Neurology. 2016; 86: 1446-1453https://doi.org/10.1212/WNL.0000000000002474
        • Lorefice L.
        • Fenu G.
        • Trincas G.
        • Moro M.F.
        • Frau J.
        • Coghe G.C.
        • Cocco E.
        • Marrosu M.G.
        • Carta M.G.
        Progressive multiple sclerosis and mood disorders.
        Neurol. Sci. 2015; 36: 1625-1631https://doi.org/10.1007/s10072-015-2220-3
        • Zabad R.K.
        • Patten S.B.
        • Metz L.M.
        The association of depression with disease course in multiple sclerosis.
        Neurology. 2005; 64: 359-360https://doi.org/10.1212/01.WNL.0000149760.64921.AA
        • de Graaf R.
        • Ten Have M.
        • van Dorsselaer S.
        The Netherlands mental health survey and incidence study-2 (NEMESIS-2): design and methods.
        Int. J. Methods Psychiatr. Res. 2010; 19: 125-141https://doi.org/10.1002/mpr.317